Primary PTH-rp secreting neuroendocrine tumours are a rare cause of humeral hypercalcaemia of malignancy. Significant elevation in PTH-rp levels is often associated with extensive metastatic disease, and associated uncontrolled hypercalcaemia leads to substantial morbidity and eventual mortality.
A 66 year old female presented with symptomatic hypercalcaemia resulting from a large PTH-rp hypersecreting pancreatic neuroendocrine tumour. The patient had marked hypercalcaemia at 4.22 mmol/L (Normal range (NR)2.1-2.55), in association with highly elevated PTH-rp levels of 55.4pmol/L (NR 0-1.5), with an 11cm pancreatic tail mass identified on imaging, without evidence of metastatic disease. Calcium levels and symptoms improved on standard therapy with bisphosphonate, calcitonin and saline hydration, however the effect was not sustained. The patient re-presented with symptomatic hypercalcaemia, this time responding only to the addition of a somatostatin analogue. This effect was also short-lived and the patient presented with hypercalcaemia refractory to saline hydration, calcitonin, octreotide, and calcium continued to rise to a maximum of 5.14 mmol/L despite haemofiltration.
Progressive symptoms lead to the need for emergent surgery, with eventual distal pancreatectomy, splenectomy and en bloc colonic resection to control calcium levels.
There is significant heterogeneity in the behaviour of PTH-rp secreting NETs, without apparent correlation between PTH-rp and calcium levels. Initial management is centred on medical intervention including hydration, bisphosphonates, calcitonin and somatostatin analogues, but ultimately surgical resection and reduction of tumour bulk is required to achieve adequate and sustained control of calcium levels. There are many mechanisms involved in escape of hypercalcaemia from standard therapy, demonstrated within this case with significant hypercalcaemia developing over several symptomatic periods with progressive resistance to treatment over a short time interval.